PROJECT SUMMARY The Cardiac Physiology and Surgical Core (Core C) will be a focal point of the program by providing the infrastructure to support numerous experimental approaches to assess cardiac physiology and pathology, in the intact animal. Utilizing the vast experience and expertise of the Co-Director's, and well developed and proven protocols for the assessment of cardioprotection in multiple animal models, the Core will not only provide a consistent and reproducible service in support of the projects but will further participate in experimental design, prioritization of resources, and the interpretation of data. In addition, Core C will identify additional areas for collaboration across all projects as the program matures and thus be central to the interactive environment and comprehensive analysis of the overall platform as data is generated. The scientific core will provide a wide-range of services pertinent to the overall success of the program including in both mouse and porcine models: delivery of novel cell-free exosome therapeutics to the myocardium, in vivo induction of ischemia/reperfusion (IR) injury, the assessment of cardiac structure and function by multiple methodologies, and histological and biochemical assessment of myocardial injury. These services will provide the backbone for the major focus of this Program Project Grant to determine the impact of exosome therapy on the molecular pathogenesis of cardiac IR-injury.